1. Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial
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Maggioni, Aldo P., Greene, Stephen J., Fonarow, Gregg C., Böhm, Michael, Zannad, Faiez, Solomon, Scott D., Lewis, Eldrin F., Baschiera, Fabio, Hua, Tsushung A., Gimpelewicz, Claudio R., Lesogor, Anastasia, Gheorghiade, Mihai, Ramos, Silvina, Luna, Alejandra, Miriuka, Santiago, Diez, Mirta, Perna, Eduardo, Luquez, Hugo, Pinna, Jorge Garcia, Castagnino, Jorge, Alvarenga, Pablo, Ibañez, Julio, Blumberg, Eduardo Salmon, Dizeo, Claudio, Guerrero, Rodolfo Ahuad, Schygiel, Pablo, Milesi, Rodolfo, Sosa, Carlos, Hominal, Miguel, Marquez, Lilia Lobo, Poy, Carlos, Hasbani, Eduardo, Vico, Marisa, Fernandez, Alberto, Vita, Nestor, Vanhaecke, Johan, De Keulenaer, Gilles, Striekwold, Harry, Vervoort, Geert, Vrolix, Mathias, Henry, Philippe, Dendale, Paul, Smolders, Walter, Marechal, Patrick, Vandekerckhove, Hans, Oliveira, Mucio, Neuenschwande, Fernando, Reis, Gilmar, Saraiva, Jose, Bodanese, Luiz, Canesin, Manoel, Greco, Oswaldo, Bassan, Roberto, Marino, Roberto Luis, Giannetti, Nadia, Moe, Gordon, Sussex, Bruce, Sheppard, Richard, Huynh, Thao, Stewart, Robert, Haddad, Haissam, Echeverria, Luis, Quintero, Adalberto, Torres, Adriana, Jaramillo, Mónica, Lopez, Mónica, Mendoza, Fernan, Florez, Noel, Cotes, Carlos, Garcia, Magali, Belohlavek, Jan, Hradec, Jaromir, Peterka, Martin, Gregor, Pavel, Monhart, Zdenek, Jansky, Petr, Kettner, Jiri, Reichert, Petr, Spinar, Jindrich, Brabec, Tomas, Hutyra, Martin, Solar, Miroslav, Pietilä, Mikko, Nyman, Kai, Pajari, Risto, Cohen, Ariel, Galinier, Michel, Gosse, Philippe, Livarek, Bernard, Neuder, Yannick, Jourdain, Patrick, Picard, François, Isnard, Richard, Hoppe, Uta, Kaeaeb, Stefan, Rosocha, Stefan, Prondzinsky, Roland, Felix, Stephan, Duengen, Hans-Dirk, Figulla, Hans-Reiner, Fischer, Sven, Behrens, Steffen, Stawowy, Philipp, Kruells-Muench, Juergen, Knebel, Fabian, Nienaber, Christoph, Werner, Dierk, Aron, Wilma, Remppis, Bjoern, Hambrecht, Rainer, Kisters, Klaus, Werner, Nikos, Hoffmann, Stefan, Rossol, Siegbert, Geiss, Ernst, Graf, Kristof, Hamann, Frank, von Scheidt, Wolfgang, Schwinger, Robert, Tebbe, Ulrich, Costard-Jaeckle, Angelika, Lueders, Stephan, Heitzer, Thomas, Leutermann-Oei, Marie-Louise, Braun-Dullaeus, Ruediger, Roehnisch, Jens-Uwe, Muth, Gerhard, Goette, Andreas, Rotter, Achim, Ebelt, Henning, Olbrich, Hans-Georg, Mitrovic, Veselin, Hengstenberg, Christian, Schellong, Sebastian, Zamolyi, Karoly, Vertes, Andras, Matoltsy, Andras, Palinkas, Attila, Herczeg, Bela, Apro, Dezso, Lupkovics, Geza, Tomcsanyi, Janos, Toth, Kalman, Mathur, Atul, Banker, Darshan, Bharani, Anil, Arneja, Jaspal, Khan, Aziz, Gadkari, Milind, Hiremath, Jagdish, Patki, Nitin, Kumbla, Makund, Santosh, M.J., Ravikishore, A.G., Abhaichand, Rajpal, Maniyal, Vijayakukmar, Nanjappa, Manjunath, Reddy, P. Naveen, Chockalingam, Kulasekaran, Premchand, Rajendra, Mahajan, Vijay, Lewis, Basil, Wexler, Dov, Shochat, Michael, Keren, Andre, Omary, Muhamad, Katz, Amos, Marmor, Alon, Lembo, Giuseppe, Di Somma, Salvatore, Boccanelli, Alessandro, Barbiero, Mario, Pajes, Giuseppe, De Servi, Stefano, Greco, Dott Cosimo, De Santis, Fernando, Floresta, Agata, Visconti, Luigi Oltrona, Piovaccari, Giancarlo, Cavallini, Claudio, Di Biase, Matteo, Masini, Dott Franco, Vassanelli, Corrado, Viecca, Maurizio, Cangemi, Dott Francesco, Pirelli, Salvatore, Borghi, Claudio, Volpe, Massimo, Branzi, Angelo, Percoco, Dott Giovanni, Severi, Silvia, Santini, Alberto, De Lorenzi, Ettore, Metra, Marco, Zacà, Valerio, Mortara, Andrea, Tranquilino, Francisco P., Babilonia, Noe A., Ferrolino, Arthur M., Manlutac, Benjamin, Dluzniewski, Miroslaw, Dzielinska, Zofia, Nowalany-Kozie, Ewa, Mazurek, Walentyna, Wierzchowiecki, Jerzy, Wysokinski, Andrzej, Szachniewicz, Joanna, Romanowski, Witold, Krauze-Wielicka, Magdalena, Jankowski, Piotr, Berkowski, Piotr, Szelemej, Roman, Kleinrok, Andrzej, Kornacewicz-Jac, Zdzislawa, Vintila, Marius, Vladoianu, Mircea, Militaru, Constantin, Dan, Gheorghe, Dorobantu, Maria, Dragulescu, Stefan, Kostenko, Victor, Vishnevsky, Alexandr, Goloschekin, Boris, Tyrenko, Vadim, Gordienko, Alexander, Kislyak, Oxana, Martsevich, Sergey, Kuchmin, Alexey, Karpov, Yurii, Fomin, Igor, Shvarts, Yury, Orlikova, Olga, Ershova, Olga, Berkovich, Olga, Sitnikova, Maria, Pakhomova, Inna, Boldueva, Svetlana, Tyurina, Tatiana, Simanenkov, Vladimir, Boyarkin, Mikhail, Novikova, Nina, Tereschenko, Sergey, Zadionchenko, Vladimir, Shogenov, Zaur, Gordeev, Ivan, Moiseev, Valentin, Wong, Raymond, Ong, Hean Yee, Le Tan, Ju, Goncalvesova, Eva, Kovar, Frantisek, Skalina, Ivan, Kasperova, Viera, Hojerova, Silvia, Szentivanyi, Miroslav, Stancak, Branislav, Babcak, Marian, Kycina, Peter, Poliacik, Pavol, Toth, Peter, Sirotiakova, Jana, de Sa, Esteban Lopez, Bueno, Manuel Gomez, Selles, Manuel Martinez, Cabrera, Jose Angel, Freire, Ramon Bover, Gonzalez Juanatey, Jose Ramon, Comin, Josep, Soriano, FranciscoRidocci, Lopez, Alejandro, Vicho, Raul, Lama, Manuel Geraldia, Schaufelberger, Maria, Brunotte, Richard, Ullman, Bengt, Hagerman, Inger, Cizinsky, Stella, Cherng, Wen-Jin, Yu, Wen-Chung, Kuo, Chi-Tai, Chang, Kuan-Cheng, Lai, Wen-Ter, Kuo, Jen-Yuan, Ural, Dilek, Badak, Ozer, Akin, Mustafa, Yigit, Zerrin, Yokusoglu, Mehmet, Yilmaz, Mehmet, Abaci, Adnan, Ebinc, Haksun, Perlman, Richard, Parish, David, Bergin, James, Burnham, Kenneth, Brown, Christopher, Lundbye, Justin, Williams, Celeste, Eisen, Howard, Juneman, Elizabeth, Joseph, Susan, Peberdy, Mary Ann, Peura, Jennifer, Gupta, Vishal, Habet, Kalim, French, William, Mody, Freny, Graham, Susan, Hazelrigg, Monica, Chung, Eugene, Dunlap, Stephanie, Nikolaidis, Lazaros, Najjar, Samer, Katz, Richard, Murali, Srinivas, Izzo, Joseph L., Callister, Tracy, Phillips, Roland, Lippolis, Nicholas, Winterton, John, Meymandi, Sheba, Heilman, Karl, Oren, Ron, Zolty, Ronald, Brottman, Michael, Gunawardena, D.R., Adams, Kirkwood, Barnard, Denise, Klapholz, Marc, Fulmer, James, Maggioni AP, Greene SJ, Fonarow GC, Böhm M, Zannad F, Solomon SD, Lewis EF, Baschiera F, Hua TA, Gimpelewicz CR, Lesogor A, Gheorghiade M, Ramos S, Luna A, Miriuka S, Diez M, Perna E, Luquez H, Pinna JG, Castagnino J, Alvarenga P, Ibañez J, Blumberg ES, Dizeo C, Guerrero RA, Schygiel P, Milesi R, Sosa C, Hominal M, Marquez LL, Poy C, Hasbani E, Vico M, Fernandez A, Vita N, Vanhaecke J, De Keulenaer G, Striekwold H, Vervoort G, Vrolix M, Henry P, Dendale P, Smolders W, Marechal P, Vandekerckhove H, Oliveira M, Neuenschwande F, Reis G, Saraiva J, Bodanese L, Canesin M, Greco O, Bassan R, Marino RL, Giannetti N, Moe G, Sussex B, Sheppard R, Huynh T, Stewart R, Haddad H, Echeverria L, Quintero A, Torres A, Jaramillo M, Lopez M, Mendoza F, Florez N, Cotes C, Garcia M, Belohlavek J, Hradec J, Peterka M, Gregor P, Monhart Z, Jansky P, Kettner J, Reichert P, Spinar J, Brabec T, Hutyra M, Solar M, Pietilä M, Nyman K, Pajari R, Cohen A, Galinier M, Gosse P, Livarek B, Neuder Y, Jourdain P, Picard F, Isnard R, Hoppe U, Kaeaeb S, Rosocha S, Prondzinsky R, Felix S, Duengen HD, Figulla HR, Fischer S, Behrens S, Stawowy P, Kruells-Muench J, Knebel F, Nienaber C, Werner D, Aron W, Remppis B, Hambrecht R, Kisters K, Werner N, Hoffmann S, Rossol S, Geiss E, Graf K, Hamann F, von Scheidt W, Schwinger R, Tebbe U, Costard-Jaeckle A, Lueders S, Heitzer T, Leutermann-Oei ML, Braun-Dullaeus R, Roehnisch JU, Muth G, Goette A, Rotter A, Ebelt H, Olbrich HG, Mitrovic V, Hengstenberg C, Schellong S, Zamolyi K, Vertes A, Matoltsy A, Palinkas A, Herczeg B, Apro D, Lupkovics G, Tomcsanyi J, Toth K, Mathur A, Banker D, Bharani A, Arneja J, Khan A, Gadkari M, Hiremath J, Patki N, Kumbla M, Santosh MJ, Ravikishore AG, Abhaichand R, Maniyal V, Nanjappa M, Reddy PN, Chockalingam K, Premchand R, Mahajan V, Lewis B, Wexler D, Shochat M, Keren A, Omary M, Katz A, Marmor A, Lembo G, Di Somma S, Boccanelli A, Barbiero M, Pajes G, De Servi S, Greco DC, De Santis F, Floresta A, Visconti LO, Piovaccari G, Cavallini C, Di Biase M, Masini DF, Vassanelli C, Viecca M, Cangemi DF, Pirelli S, Borghi C, Volpe M, Branzi A, Percoco DG, Severi S, Santini A, De Lorenzi E, Metra M, Zacà V, Mortara A, Tranquilino FP, Babilonia NA, Ferrolino AM, Manlutac B, Dluzniewski M, Dzielinska Z, Nowalany-Kozie E, Mazurek W, Wierzchowiecki J, Wysokinski A, Szachniewicz J, Romanowski W, Krauze-Wielicka M, Jankowski P, Berkowski P, Szelemej R, Kleinrok A, Kornacewicz-Jac Z, Vintila M, Vladoianu M, Militaru C, Dan G, Dorobantu M, Dragulescu S, Kostenko V, Vishnevsky A, Goloschekin B, Tyrenko V, Gordienko A, Kislyak O, Martsevich S, Kuchmin A, Karpov Y, Fomin I, Shvarts Y, Orlikova O, Ershova O, Berkovich O, Sitnikova M, Pakhomova I, Boldueva S, Tyurina T, Simanenkov V, Boyarkin M, Novikova N, Tereschenko S, Zadionchenko V, Shogenov Z, Gordeev I, Moiseev V, Wong R, Ong HY, Le Tan J, Goncalvesova E, Kovar F, Skalina I, Kasperova V, Hojerova S, Szentivanyi M, Stancak B, Babcak M, Kycina P, Poliacik P, Toth P, Sirotiakova J, Lopez de Sa E, Bueno MG, Selles MM, Cabrera JA, Freire RB, Gonzalez Juanatey JR, Comin J, Soriano F, Lopez A, Vicho R, Lama MG, Schaufelberger M, Brunotte R, Ullman B, Hagerman I, Cizinsky S, Cherng WJ, Yu WC, Kuo CT, Chang KC, Lai WT, Kuo JY, Ural D, Badak O, Akin M, Yigit Z, Yokusoglu M, Yilmaz M, Abaci A, Ebinc H, Perlman R, Parish D, Bergin J, Burnham K, Brown C, Lundbye J, Williams C, Eisen H, Juneman E, Joseph S, Peberdy MA, Peura J, Gupta V, Habet K, French W, Mody F, Graham S, Hazelrigg M, Chung E, Dunlap S, Nikolaidis L, Najjar S, Katz R, Murali S, Izzo JL, Callister T, Phillips R, Lippolis N, Winterton J, Meymandi S, Heilman K, Oren R, Zolty R, Brottman M, Gunawardena DR, Adams K, Barnard D, Klapholz M, and Fulmer J
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Male ,medicine.medical_specialty ,Cardiotonic Agents ,ASTRONAUT ,Diabetic Cardiomyopathies ,Administration, Oral ,Kaplan-Meier Estimate ,Placebo ,Diabete ,chemistry.chemical_compound ,Double-Blind Method ,Fumarates ,Internal medicine ,Diabetes mellitus ,Troponin I ,Renin ,Clinical endpoint ,medicine ,Humans ,Prospective Studies ,Heart Failure ,Ejection fraction ,business.industry ,Surrogate endpoint ,Aliskiren ,Middle Aged ,medicine.disease ,Amides ,Hospitalization ,Endocrinology ,Death, Sudden, Cardiac ,Treatment Outcome ,chemistry ,Heart failure ,Female ,Cardiology and Cardiovascular Medicine ,business ,aliskiren - Abstract
Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether alis- kiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post- discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B- type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P ¼ 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P ¼ 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P , 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldoster- one relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P ¼ 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without DM.
- Published
- 2013